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Protein Kinase G Regulated H 2 S Governs Oxygen Sensing by the Carotid Body
Author(s) -
Kumar Ganesh,
Yuan Guoxiang,
Peng YingJie,
Makarenko Vladislav,
Raghuraman Gayatri,
Nanduri Jayasri,
Vasavda Chirag,
Gadalla Moataz,
Snyder Solomon,
Prabhakar Nanduri
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.682.2
Subject(s) - chemistry , carbon monoxide , heme , heme oxygenase , carotid body , phosphorylation , serine , carbonyl sulfide , protein kinase a , kinase , biophysics , oxygen , signal transduction , hydrogen sulfide , biochemistry , catalysis , enzyme , sulfur , medicine , biology , carotid arteries , organic chemistry
Previous studies showed that O 2 sensing by the carotid body (CB) requires carbon monoxide (CO) generation by heme oxygenase (HO)‐2 and hydrogen sulfide (H 2 S) synthesis by cystathionine‐γ‐lyase (CSE). However, the mechanism(s) underlying O 2 ‐dependent gaseous messenger generation are not known. Here, we report that CO but not H 2 S generation is sensitive to changes in O 2 levels. The O 2 ‐dependent CO generation requires two cysteine residues (C265 and C282) located in the heme‐regulatory motif of HO‐2. Carbon monoxide, in turn inhibits H 2 S generation from CSE via protein kinase G (PKG)‐dependent phosphorylation of serine 377. Hypoxia, by reducing CO generation, decreases the inhibition of CSE resulting in elevated H 2 S, which mediates the increased CB neural activity. These results demonstrate that PKG‐dependent regulation of H 2 S governs O 2 sensing by the carotid body (Supported by NIH‐HLBI PO1 HL‐090554).